Function and Specificity of γ/δ T Cells

Current Topics in Microbiology and Immunology

Book 173
Springer Science & Business Media
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Our current understanding of a/~ T cell receptor (TCR) ex pressing T cells advanced from function and specificity to the molecular organization ofthe TCR.We now know that the TCR a and ~ chains together express specificity for (antigenic) peptides presented by the "responder" M H C allele, thus explain ing the phenomenon of MHC restriction at a molecular level. Surprisingly even though our perception of the molecular organization of the y5 TCR is well advanced, current knowledge of function and specificity of the y5 T cell subset is poor. There fore it appeared rather timely to bring together scientists pioneering research on y5 T cells forthe International Workshop on Function and Specificity ofy5 Tcells,held October11-14, 1990 at Schloss Elmau/Bavaria, FRG. Besides offering a scientific forum for open discussions, it was also hoped that such a workshop would be seminal for collaborative interactions and personal relationships among scientists "addicted" to y 15 T cells.
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Publisher
Springer Science & Business Media
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Published on
Dec 6, 2012
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Pages
296
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ISBN
9783642764929
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Best For
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Language
English
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Genres
Medical / General
Medical / Immunology
Medical / Microbiology
Science / Life Sciences / Cell Biology
Science / Life Sciences / Molecular Biology
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ADP-ribosylating toxins have been the focus of intensive research for more than 30 years. Researchers from diverse fields of science have taken an interest in these bacterial toxins; they are studied, for example, by microbiologists, biochemists, cell biologists, and pharmacologists. There are two principal reasons for the broad and still growing interest in ADP ribosylating toxins. First, insights into the structure and functions of the toxins might be the key to prevention and treatment of diseases caused by the toxin-producing infectious micro organisms. Second, the ADP-ribosylating toxins provide potent and often unique pharmacological tools for the study of the physiological functions of their target proteins. The latter is especially the case with cholera and pertussis toxins, which both modify the IX-subunits of heterotrimeric G-proteins involved in signal transduction pathways. These toxins have proved invaluable in extending our basic understanding of the regulation of hormone-controlled signal transduction. This volume provides a review and an update of recent studies on the basic properties of bacterial ADP-ribosylating tbxins and/or exoenzymes. Our current knowledge of the cel lular entry mechanisms of ADP-ribosylating toxins is reviewed by MADSHUS and STENMARK. WILSON and COLLIER then deal with recent insights into the enzyme mechanism and active site structure of diphtheria toxin and Pseudomonas aeruginosa exotoxin A, which modify elongation factor 2. Toxins which ADP-ribosylate heterotrimeric G-proteins involved in trans membrane signal transduction are the subject of the next two chapters.
Many RNA viruses have been known for decades to be genetically and biologically quite variable. Some well-known examples are influenza viruses, foot and mouth disease viruses, and Newcastle disease virus. During the past decade, it has become clear that most, it not all. , RNA viruses (riboviruses and retroviruses) are much more mutable than was recognized previously, and that this great mutability generates extremely complex populations consisting of indeterminate mixtures of related variants (Le. , "mutant swarms" or "quasispecies" populations). This is also true of DNA viruses (such as hepatitis DNA genomes via RNA transcripts B virus) which replicate their that are reverse-transcribed back to DNA. This hypermutability of RNA replicons provides great biological adaptability for RNA virus genomes. It also allows (but does not necessitate) RNA viruses, so that they can extremely rapid evolution of evolve over a million times more quickly than their eukaryotic DNA-based hosts. The genetics of RNA replicons is so unusual (and often counterintuitive) that it has many important biological conse quences which are neither readily apparent nor widely under stood. Failure to understand the distinctive aspects of RNA genetics frequently generates confusion and controversy and can adversely impact vaccine and antiviral drug programs and other applications of medical virology. The 14 chapters in this volume describe advances in a number of significant areas of RNA virus genetics and evolution.
Most lymphocytes recirculate throughout the body, migrating from blood through organized lymphoid tissues such as lymph nodes (LN) and Peyer's patches (PP), then to lymph and back to blood (GOWANS and KNIGHT 1964). Smaller numbers of lymphocytes migrate from blood to extranodal tissues such as pancreas and then through lymphatic vessels to LN (MACKAY et al. 1990). An important feature of this migration is the ability of lymphocytes to recognize and adhere to the surface of blood vessel endothelial cells before migrating through the vessel wall into surrounding tissue (CARLOS and HARLAN 1994; IMHOF and DUNON 1995; BUTCHER and PICKER 1996). Adhesion interactions of vascular endothelium with lymphocytes under flow or shear consist of at least four steps: (I) an initial transient sticking or rolling; (2) if the lymphocytes encounter appropriate activating or chemotactic factors in the local environment, rolling may be followed by a lymphocyte activation step that then leads to; (3) strong adhesion or sticking that may be followed by; (4) lym phocyte diapedesis into tissue (BUTCHER 1991; SHIMUZU et al. 1992; SPRINGER 1994; BARGATZE et al. 1995). Specific lymphocyte and endothelial adhesion molecules (AM) are involved in each step of this "adhesion cascade" (reviewed in CARLOS and HARLAN 1994; IMHOF and DUNON 1995; BUTCHER and PICKER 1996). This allows lymphocyte migration to be controlled at several different steps, leading to a combinatorial increase in specificity and sensitivity.
Severe sepsis and septic shock are the most serious compli cations of bacterial infections. Both gram-positive and gram negative bacteria can trigger these extreme inflammatory re sponses and, by so doing, cause substantial morbidity and mortality. In the United States alone, over 400 000 patients suffer from septicaemia each year, and approximately 100 000 of these patients die despite optimal intensive care and modern antimicrobial therapy. These dramatic figures have prompted intensive research to define the bacterial and host factors involved in the septic response. Scientists from many disciplines, including chem istry, physics, biology, medical microbiology, immunology, and pharmacology, have worked closely with clinicians to achieve rapid and profound progress. To translate this newly acquired knowledge into clinical practice, clinical trials have also been performed to evaluate numerous new therapeutic drugs. The disappointing results from these trials have underscored a major lesson, namely, that sepsis constitutes an extremely complex syndrome and that basic and clinical research must be greatly intensified in order to illuminate its molecular mechan isms. At this stage, the editors of the present volume of Current Topics in Microbiology and Immunology considered it would be rewarding to compile a volume summarizing our present basic and clinical knowledge on sepsis. Our particular gratitude extends to those international experts who have followed our invitation and elaborated on particular areas of the basic and clinical aspects of this field.
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